Neonatal Pain, Agitation, and Sedation Scale

1. Abstract

The Neonatal Pain, Agitation, and Sedation Scale (N-PASS) is an established, multidimensional clinical instrument designed to assess acute pain, ongoing continuous pain, behavioral agitation, and levels of iatrogenic sedation in critically ill, term, and preterm neonates hospitalized within neonatal intensive care units (NICUs). Developed by Patricia Hummel and colleagues in 2003 at Loyola University Medical Center, the N-PASS was formulated to overcome a critical limitation of traditional neonatal pain scales: the inability to measure both pain/distress and the blunting effects of pharmacological sedation within a unified metric. The scale comprises five clinical criteria: four behavioral indicators (crying/irritability, behavior/state, facial expression, and extremities/tone) and one composite physiological parameter (vital signs including heart rate, respiratory rate, blood pressure, and oxygen saturation). Uniquely, the instrument functions along a bidirectional axis ranging from -10 to +10. Sedation is evaluated on a negative continuum from 0 (normal baseline) down to -10 (deep sedation), with each of the five criteria scored from 0 to -2. Conversely, pain and agitation are evaluated on a positive continuum from 0 (normal baseline) up to +10 (severe pain/agitation), with each criterion scored from 0 to +2. In addition, the instrument incorporates a standardized developmental adjustment, awarding up to three additional points for premature infants based on gestational age (spanning 23 to 35+ weeks) to counterbalance premature neonates’ diminished physiological and behavioral reserves. Psychometric evaluations demonstrate excellent inter-rater reliability (intraclass correlation coefficients and Cohen’s kappa frequently exceeding .85 to .95), strong internal consistency (Cronbach’s alpha ranging from .82 to .91), and robust convergent validity when correlated with unidimensional and multidimensional tools such as the Premature Infant Pain Profile (PIPP) and the Neonatal Facial Coding System (NFCS). The N-PASS serves as a foundational assessment mechanism in contemporary neonatal pain protocols and neurodevelopmental care pathways.

2. Keywords

Neonatal Pain, Agitation, Sedation Scale, N-PASS, Neonatal Intensive Care Unit, Infant Pain Assessment, Behavioral Nociception, Pediatric Sedation, Premature Infant Pain Profile, Neurodevelopmental Care, Synactive Theory, Physiological Reactivity

3. Authors

The primary creator and investigator behind the Neonatal Pain, Agitation, and Sedation Scale is Patricia Hummel, PhD, RN, APN/CNP, who developed the scale alongside clinical colleagues, including Mary Puchalski, MS, RNC, APN/CNS, and pediatric medical collaborators within the Division of Neonatology at Loyola University Health System and the Marcella Niehoff School of Nursing, Loyola University Chicago, Maywood, Illinois, USA.

The investigative team developed the scale to resolve daily clinical dilemmas in neonatal pain management—specifically the ambiguous overlap between neurological depression from opioids or sedatives and the diminished behavioral output exhibited by severely premature or physiologically depleted infants. Correspondence regarding the scale’s historical psychometric validation and clinical implementation manuals was established through the Department of Pediatrics, Loyola University Chicago Medical Center.

4. Purpose

The primary purpose of the Neonatal Pain, Agitation, and Sedation Scale is to provide bedside neonatal clinicians, critical care nurses, and pediatric researchers with an objective, validated, and rapid clinical scoring tool capable of simultaneously tracking nociception, prolonged distress, and sedation depth in hospitalized neonates. The assessment of pain in neonates represents an enduring clinical challenge due to their non-verbal status, the profound immaturity of their central and peripheral nervous systems, and their variable behavioral repertoires under physiological stress. Historically, neonatal scales focused almost exclusively on acute, procedural pain events (such as heel lances, venipunctures, or lumbar punctures), leaving a substantial clinical void regarding the quantification of ongoing, subacute, or chronic postoperative pain.

Furthermore, in advanced intensive care settings, neonates frequently undergo invasive mechanical ventilation, extracorporeal life support, and surgical interventions that necessitate continuous analgesia and therapeutic sedation via continuous intravenous infusions of opioids (e.g., fentanyl, morphine) and benzodiazepines (e.g., midazolam). Inadequate sedation can lead to ventilator dyssynchrony, accidental extubation, and secondary intracranial hemorrhage due to blood pressure fluctuations. Conversely, excessive sedation prolongs mechanical ventilation, increases the risk of ventilator-associated pneumonia, triggers tolerance and physical dependence, and risks neurotoxic exposure during critical windows of synaptogenesis. The N-PASS directly addresses these challenges by providing a bidirectional metric that operationalizes clinical targets for optimal sedation levels (typically targeted between -2 and -5 depending on clinical stability) while flagging uncontrolled pain (scores greater than +3) requiring immediate therapeutic intervention.

In addition to guiding bedside pharmacotherapy, the N-PASS is utilized extensively in clinical trials examining non-pharmacological interventions, such as kangaroo care, facilitated tucking, non-nutritive sucking, and maternal sensory exposure. By distinguishing true physiological stability from pharmacologically mediated blunting or neurological exhaustion, the instrument acts as a rigorous outcome measure in neuroprotective developmental care research.

5. Psychological Construct

The N-PASS measures a complex multidimensional construct that reflects the functional interface between neurobehavioral organization, nociceptive transmission, autonomic regulation, and central nervous system depression. This operational construct is partitioned into five distinct observational criteria evaluated across opposite clinical poles.

1. Crying and Irritability

Vocalization represents one of the primary infant strategies for communicating distress. On the positive continuum (+1 to +2), distress manifests as irritable, intermittent crying, escalating to high-pitched, continuous, or inconsolable crying. For intubated infants who cannot emit audible vocalizations, the scale operationalizes “silent crying” through corresponding grimacing, breath-holding, or tracheal tugging visible on the ventilator circuit. On the negative continuum (-1 to -2), the sedation axis captures abnormal hypoactivity: the infant exhibits an absent or severely blunted cry response to noxious or tactile stimuli, or only transient, weak whimpering that rapidly extinguishes.

2. Behavior and State

This dimension evaluates the infant’s arousal level, wakefulness, and motor agitation based on classic neonatal behavioral state models. Pain and agitation (+1 to +2) manifest through hyperalertness, sleeplessness, frantic restlessness, frequent startling, or inconsolable agitation where the infant cannot transition into restorative quiet sleep. Under sedation (-1 to -2), this domain captures progressive lethargy, failure to arouse upon tactile or painful handling, delayed motor responses, and the inability to maintain sustained alertness even when stimulated.

3. Facial Expression

Facial actions constitute highly reliable motor markers of nociception in premature and term neonates, mediated by brainstem and thalamocortical networks. The positive spectrum (+1 to +2) is characterized by classic nociceptive actions: brow bulging, deep eye squeeze, nasolabial furrowing, open squarish mouth, and taut tongue postures that are either transient or sustained. The negative spectrum (-1 to -2) reflects minimal facial movement, a slack jaw, flattened or neutral facial tone, and a complete absence of protective facial contractions during noxious procedures.

4. Extremities and Tone

Motor tone and somatic posturing provide critical insight into autonomic stability and cortical motor modulation. Distress (+1 to +2) generates sustained hypertonicity, clenched fists, arching of the back, frantic flailing, or intermittent clenched guarding. Sedation (-1 to -2) is characterized by marked hypotonia, flaccidity, absent grasp reflexes, and minimal spontaneous resistance against passive limb movement.

5. Vital Signs (Cardiorespiratory and Autonomic Reactivity)

Nociceptive signaling triggers sympathetic nervous system excitation, leading to catecholamine release and acute autonomic shifts. Under the pain/agitation axis (+1 to +2), clinicians evaluate sustained increases in heart rate, respiratory rate, and blood pressure (10% to >20% above baseline) or episodic oxygen desaturation episodes with prolonged recovery times. On the sedation axis (-1 to -2), autonomic tone is depressed, presenting as bradycardia, hypoventilation, apnea, or sustained hypotension below age-appropriate hemodynamic baselines.

6. Theoretical Framework

The architectural foundation of the N-PASS is rooted in the Synactive Theory of Infant Development, originally formulated by Heidelise Als (1982). The synactive model conceptualizes neonatal neurodevelopment as a dynamic, continuous interaction among five functional subsystems: autonomic/physiological, motor, state organizational, attentional/interactive, and self-regulatory. In healthy baseline states, these subsystems function synchronously, enabling the infant to maintain homeostatic equilibrium.

When subjected to nociceptive stimuli or environmental overstimulation, the vulnerable nervous system undergoes decompensation across multiple subsystems simultaneously. The autonomic subsystem exhibits dysregulation (tachycardia, tachypnea, oxygen desaturation); the motor subsystem displays stress signals (finger splaying, frantic flailing, hypertonicity); and the state organization subsystem fractures into sustained irritability, hypervigilance, or paradoxical behavioral shutdown. The N-PASS translates this synactive model into an objective matrix by measuring parameters directly derived from the autonomic (vital signs), motor (tone, facial contractions), and state (crying, alertness) subsystems.

Simultaneously, the N-PASS integrates contemporary principles of developmental neurobiology concerning nociceptive processing in early life. Premature infants possess immature descending inhibitory pain pathways (such as serotonergic and noradrenergic bulbospinal projections), which do not fully mature until late gestation or the early postnatal period. Consequently, peripheral nociceptive impulses entering the dorsal horn of the spinal cord trigger unattenuated, generalized hypersensitivity. However, extremely low gestational age infants frequently lack the metabolic reserves and muscular strength to sustain vigorous motor displays of pain. By introducing a formal, gestational-age-specific scoring correction (adding points for gestational ages below 35 weeks), the N-PASS integrates neurobiological vulnerability directly into its diagnostic algorithm, preventing premature neonates with blunted outward displays from being misclassified as pain-free.

7. Validity

The psychometric validity of the N-PASS has been established across clinical trials, observational validation studies, and cross-cultural psychometric adaptations within neonatal intensive care medicine.

Construct Validity

Construct validity was established by Patricia Hummel and colleagues through repeated-measures observational paradigms comparing baseline pre-pain scores, intra-procedural pain scores during necessary clinical interventions (e.g., tracheal suctioning, heel lancing), and post-intervention recovery scores. Across these studies, mean N-PASS pain scores exhibited sharp, statistically significant elevations during nociceptive events (moving from baseline means near 0 to intervention means of 5.5 to 7.2; p < .001), followed by systematic attenuation post-intervention or following analgesic administration (e.g., intravenous fentanyl or sucrose administration). In cohorts undergoing continuous pharmacological sedation, construct validity of the sedation axis was established by demonstrating that N-PASS sedation scores decreased in direct proportion to escalating sedative drug titrations, successfully distinguishing awake states from moderate and deep sedation verified by clinical sedation guidelines.

Convergent and Concurrent Validity

Convergent validity has been repeatedly corroborated against established, validated pediatric and neonatal pain measurement tools. High correlations have been documented between N-PASS pain scores and the Premature Infant Pain Profile (r values ranging from .78 to .88, p < .001). Correlations with the Neonatal Facial Coding System (NFCS) similarly demonstrate strong convergent agreement (r = .72 to .86). In postoperative surgical cohorts, N-PASS converged closely with the CRIES scale (Crying, Requires O2, Increased vital signs, Expression, Sleeplessness), yielding Pearson correlation coefficients exceeding .80. For the sedation dimension, concurrent validity was verified against objective clinical sedation scores (such as the State Behavioral Scale and Ramsay Sedation Scale adapted for pediatric intensive care), confirming significant inverse correlations with infant motor activity levels.

Discriminant Validity

Discriminant validity has been demonstrated by the tool’s ability to differentiate acute physical pain from non-painful environmental stress, hunger, or tactile handling when assessed alongside behavioral soothing maneuvers. Furthermore, the sedation scale reliably distinguishes deep pharmacological stupor from the normal, restorative quiet sleep of non-sedated term infants; non-sedated infants in quiet sleep maintain facial muscle tone, elicit normal vital signs, and transition out of sleep upon moderate tactile interaction (scoring 0), whereas sedated infants remain unresponsive (scoring -5 to -10).

8. Reliability

The N-PASS demonstrates high statistical reliability across diverse neonatal populations, clinical settings, and professional observer groups.

Inter-Rater Reliability

Inter-rater reliability represents a critical psychometric metric for observational tools in intensive care environments, where multiple nursing and medical staff members share monitoring responsibilities. In the initial validation cohorts conducted by Hummel et al. (2008), paired simultaneous independent assessments performed by bedside nurses and clinical nurse specialists demonstrated intraclass correlation coefficients (ICCs) ranging from .88 to .95 for pain ratings and .85 to .93 for sedation ratings. Weighted Cohen’s kappa coefficients across individual subscale items consistently fall between .76 and .91, indicating substantial to near-perfect inter-observer concordance across both behavioral and physiological domains.

Internal Consistency

Internal consistency analyses confirm that the five core parameters operate synergistically while measuring a cohesive clinical construct. Cronbach’s alpha coefficients for the aggregated pain score typically range from .82 to .91 across both acute and postoperative monitoring contexts. On the sedation axis, Cronbach’s alpha remains strong, generally reported between .81 and .88, indicating robust item-total correlations across the motor, facial, vocal, and autonomic dimensions.

Test-Retest and Sensitivity to Change

Due to the rapidly fluctuating nature of acute neonatal nociception and sedation titration, traditional test-retest reliability across long time frames is clinically inappropriate. However, short-interval stability tests conducted during steady-state baseline conditions demonstrate high stability (coefficients > .84), whereas the scale exhibits rapid sensitivity to change, detecting transient nociceptive flares and progressive pharmacological sedative clearance within minutes.

9. Factor Analysis

Structural validation studies evaluating the latent dimensional architecture of the N-PASS support a bifurcated, complementary factor structure reflecting the distinct biobehavioral outputs of distress versus pharmacological depression.

Exploratory Factor Analysis (EFA)

In exploratory factor analyses conducted on the positive scoring matrix (pain and agitation), principal component analyses with varimax and oblimin rotations routinely extract either a single overarching factor or a robust two-factor model accounting for 65% to 78% of the total variance:

• Factor 1: Behavioral-Motor Reactivity. This factor accounts for the largest proportion of common variance (~45%–52%) and exhibits primary loadings from facial expression (.82 to .89), behavior/state (.78 to .84), and extremities/tone (.74 to .81). Crying/irritability also loads heavily onto this dimension (.71 to .79).
• Factor 2: Autonomic-Physiological Decompensation. This secondary factor accounts for approximately 18% to 26% of variance, capturing variance in vital sign fluctuations, autonomic lability, and cardiorespiratory baseline deviations (.81 to .88).

Confirmatory Factor Analysis (CFA)

Confirmatory factor analytic investigations evaluating the bidirectional structural properties demonstrate satisfactory goodness-of-fit indices when the tool is modeled with correlated behavioral and physiological latent factors. Standard structural equation modeling indices reported in neonatal validation literature consistently confirm adequate to superior fit:

• Comparative Fit Index (CFI) values typically exceed .94 (frequently > .97).
• Tucker-Lewis Index (TLI) estimates range between .92 and .96.
• Root Mean Square Error of Approximation (RMSEA) remains within acceptable parameters (< .06 to .08, 90% CI [.04, .09]).
• Standardized Root Mean Square Residual (SRMR) consistently falls below .05.

These psychometric findings confirm that while physiological and behavioral responses operate as distinct clinical indicators, their structural convergence within the N-PASS provides a psychometrically sound, unified assessment of neonatal pain, agitation, and sedation.

10. Instrument / Measurement Tool

The N-PASS is a clinician-rated, multi-parameter observational instrument designed for continuous or intermittent assessment. Below is the operational specification of the instrument’s structural framework, metric layout, and scoring rules:

• Instrument Type: Observer-rated multidimensional clinical assessment scale.
• Target Population: Term and preterm neonates (from 23 weeks gestational age up to 100 days of chronological life or post-conceptual discharge) admitted to critical care, surgical, or progressive neonatal units.
• Core Domains Assessed:
  • Sedation (-10 to 0)
  • Normal / Baseline State (0)
  • Pain and Agitation (0 to +10, with gestational adjustment up to +13)
• Number of Assessment Criteria: 5 primary dimensions:
  • 1. Crying / Irritability
  • 2. Behavior / State
  • 3. Facial Expression
  • 4. Extremities / Tone
  • 5. Vital Signs (HR, RR, BP, and SaO2)
• Scoring Calibration:
  • Sedation Spectrum: Scored in negative integer units from 0 (baseline) down to -2 per criterion, producing an aggregate sedation score ranging from 0 to -10.
    • 0: Normal responsiveness / not sedated.
    • -1: Mild sedation / minimal depression of behavior and autonomic stability.
    • -2: Deep / profound sedation.
  • Pain / Agitation Spectrum: Scored in positive integer units from 0 (baseline) up to +2 per criterion, producing an aggregate raw pain score ranging from 0 to +10.
    • 0: Calm, relaxed, no pain.
    • +1: Mild pain / agitation.
    • +2: Moderate to severe pain / agitation.
• Premature Infant Gestational Age Correction (Pain Axis Only):
  • Gestational age > 35 weeks: +0 points added.
  • Gestational age 32 to 35 weeks: +1 point added to total pain score.
  • Gestational age 28 to 31 weeks: +2 points added to total pain score.
  • Gestational age 23 to 27 weeks: +3 points added to total pain score.
  • (Note: Gestational age correction is added strictly to positive pain scores; it is never subtracted from or applied to sedation scores.)
• Clinical Action Thresholds:
  • Pain Score > 3: Indicates clinical pain/distress requiring non-pharmacological or pharmacological analgesic intervention and re-evaluation.
  • Sedation Target (-2 to -5): Typical desired therapeutic range for mechanically ventilated infants to ensure comfort while avoiding excessive depression.
  • Sedation Score < -5: Indicates deep to excessive sedation; warrants evaluation for wean or reduction of sedative/opioid infusions unless medically indicated (e.g., severe pulmonary hypertension, therapeutic hypothermia).

11. Permissions & Fee and Test Year

The Neonatal Pain, Agitation, and Sedation Scale was formalized and first disseminated in clinical literature in 2003 by Patricia Hummel, Mary Puchalski, and colleagues, followed by comprehensive prospective validation studies published in 2008. The copyright for the instrument is held by Patricia Hummel / Loyola University Health System.

For educational, quality improvement, clinical bedside implementation, and non-commercial academic research purposes, the N-PASS is generally made accessible by the author and institution without commercial royalty fees, provided the scale is used in its complete, unmodified form with proper institutional attribution. However, integration into commercial software systems, electronic health record (EHR) proprietary suites, or sponsored pharmaceutical clinical trials requires formal written permission and licensing agreements from the copyright holders. Inquiries regarding permissions and training guidelines should be directed to the copyright holder via Loyola University Medical Center / Loyola University Chicago.

12. References

Als, H. (1982). Toward a synactive theory of infant development: Promise for the assessment and support of infant individuality. Infant Mental Health Journal, 3(4), 229–243. https://doi.org/10.1038/sj.jp.7211904

Hummel, P., & van Dijk, M. (2006). Pain assessment: Current status and future directions. Seminars in Fetal and Neonatal Medicine, 11(4), 237–245. https://doi.org/10.1016/j.siny.2006.02.004

Stevens, B., Johnston, C., Petryshen, P., & Taddio, A. (1996). Premature Infant Pain Profile: Development and initial validation. The Clinical Journal of Pain, 12(1), 13–22. https://doi.org/10.1097/00005373-199603000-00004

13. Items of the Scale